Biomedical subjects

M Komori

Publications and source records attributed to M Komori.

At least 55 records · Page 3Linked to original sources

PubMed1995

Evidence for an increased intracellular free calcium concentration in platelets of bronchial asthma patients.

The pathogenesis of bronchial asthma is not yet fully understood. Recently much attention has been given to the hypothesis that intracellular free calcium ([Ca2+]i) metabolism is abnormal in various diseases. In this study we investigated whether [Ca2+]i exists abnormally in subjects with bronchial asthma. The [Ca2+]i in 32 treated or untreated subjects with bronchial asthma were compared with 63 normal subjects. Resting levels of [Ca2+]i were estimated by loading the fluorescent indicator Fura-2 in washed platelets. The [Ca2+]i level in the control subjects was 129.7 +/- 18.0 nM (mean +/- SD). However, in that of the bronchial asthma patients was 152.7 +/- 44.1 nM, significantly higher than that of the control subjects (p < 0.05). It is well recognized that an increase of [Ca2+]i in vascular smooth muscle involves contraction. The findings suggest that the same phenomenon is quite possible in the tracheal smooth muscle and that it plays an important role in the pathogenesis of bronchial asthma.

Adult↗

PubMed1995

Effect of iron as a new type of phosphate binder in hemodialysis patients.

Hyperphosphatemia is one of the major problems requiring management in the majority of hemodialysis patients and they require phosphate-binding agents to control the hyperphosphatemia. Aluminum hydroxide and calcium compounds are used currently as phosphate-binding agents to treat hyperphosphatemia, but these compounds can cause undesirable side effects. Therefore, the development of new phosphate-binding agents is imperative. It is well known that oral and intravenous administration of iron causes hypophosphatemia. We hypothesized that this side effect of iron may be beneficial for the treatment of hyperphosphatemia in hemodialysis patients. Consequently, we conducted a fundamental and clinical investigation of the effects of iron administration. Membrane permeability of phosphorus in a mixture of sodium ferrous citrate and dessicated aluminium hydroxide in the presence of hydrogenated lecithin as a phosporic compound was examined. Fifteen patients undergoing hemodialysis were treated with 150 mg of sodium ferrous citrate given orally for eight weeks. The permeability of the filtering membrane to phosphorus decreased in accordance with the dosage of sodium ferrous citrate and dessicated aluminum hydroxide. The degree of phosphate-binding effect of sodium ferrous citrate was larger than that of dessicated aluminum hydroxide. Serum phosphorus decreased significantly during the experiment. These results suggest that the oral administration of sodium ferrous citrate as a new phosphate binder is a useful therapeutic method for hemodialysis in patients with hyperphosphatemia.

Administration, Oral↗

PubMed1995

New aerodynamic aspects of nasal patency.

In considering possible aerodynamic indicators of subjective nasal stuffiness, we measured nasal resistance, acceleration change of nasal airflow, and alteration of differential pressure and compared those with the degree of severity of sensation of nasal obstruction in 75 patients. The acceleration change of airflow and alteration of differential pressure are presented as an equation: y = ax2 + bx + c, in which "a" represents the approximate shape of the curve. Nasal resistance, on either inspiration or expiration, and coefficient "a" of acceleration change the rapid phase from inspiration to expiration correlated well with subjective nasal patency, while coefficient "a" of acceleration change the rapid phase from expiration to inspiration and alteration of differential pressure either the rapid phase from inspiration to expiration or from expiration to inspiration did not correlate well with perception of nasal blockage. It seems that measurement of respiratory acceleration of airflow of quiet nasal breathing is a useful indicator of subjective nasal patency.

Acceleration↗

PubMed1995

[Computerized three-dimensional reconstruction of human embryos and their organs using the "NIH image" software].

Three-dimensional structures of human embryos and their internal organs were reconstructed on a CRT from their serial histological sections using a free computer software system "NIH Image." It was possible to rotate the computer images on CRT and to make cut models on any desired plane. In addition, various developmental changes could be animated by artificial "morphing" between the models at different stages. Computer graphic modeling should be of great value in the study of normal and abnormal morphogenesis. The "NIH Image" software is freely available via computer networks and has a lot of advantages over previously developed software programs used for three-dimensional reconstruction.

Computer Graphics↗

PubMed1995

A computer simulation of motion in turbo FLASH imaging and echo-planar imaging.

We have experimentally demonstrated motion effects in a turbo FLASH imaging (TFI) using a small cylindrical phantom moving at constant velocity. To further verify these experimental results, image blurring is assessed by using a computer simulation in this study. By applying the same acquisition parameters as phantom experiments, the simulation images are reconstructed to compare with the experimental results. Several kinds of configurations are applied to the simulation of the TFI. A computer simulation of an echo-planar imaging (EPI) is also used to compare the motion effects with TFI.

Computer Simulation↗

PubMed1995

Quantitative comparison of human computer interaction for direct prescription entry systems.

An objective and quantitative method is described for evaluating human-computer interaction (interface) in a direct prescription entry system. This method is based on a GOMS model and represented by a tree structure. Three different interfaces at university hospitals were compared by this evaluation method, and the differences among them were measured.

Clinical Pharmacy Information Systems↗

PubMed1995

Virtual embryology: a 3D library reconstructed from human embryo sections and animation of development process.

The volumetric shape of a human embryo and its development is hard to comprehend as they have been viewed as a 2D schemes in a textbook or microscopic sectional image. In this paper, a CAI and research support system for human embryology using multimedia presentation techniques is described. In this system, 3D data is acquired from a series of sliced specimens. Its 3D structure can be viewed interactively by rotating, extracting, and truncating its whole body or organ. Moreover, the development process of embryos can be animated using a morphing technique applied to the specimen in several stages. The system is intended to be used interactively, like a virtual reality system. Hence, the system is called Virtual Embryology.

Computer Simulation↗

PubMed1994

Comparison of heme environment at the putative distal region of P-450s utilizing their external and internal nitrogenous ligand bound forms.

Thr-303 to Lys-mutated P-450 2E1, as well as Thr-301 to Lys-mutated P-450 2C2, had absorption spectra characteristic of a nitrogenous ligand-bound form of P-450, such as the pyridine complex of P-450 2E1; (i) in the ferric state, the red-shifted Soret band, compared with the typical low-spin type spectrum of P-450, and the more intense beta band than the alpha band and (ii) in the ferrous state, two Soret peaks at around 447 and 422 nm, the relative intensities of which depended on pH, indicating the existence of two interconvertible states. The equilibrium between the two states of the mutated P-450 2E1 appeared to be shifted toward the 422 nm state, compared with the mutated P-450 2C2. The corresponding mutant of P-450 2C14 had similar spectral properties to those of both mutated P-450s except that the shorter of the two Soret bands of its ferrous form was relatively broad and appeared at 418 nm. These findings suggest that the epsilon-amino-nitrogen of the Lys of the mutated P-450s is located in the appropriate position to occupy the sixth coordination position with the heme iron and spatial differences exist in the essentially conserved structure of the distal heme domain among the three ferrous Lys-mutated P-450s.

Base Sequence↗

PubMed1994

Different mechanisms of regioselection of fatty acid hydroxylation by laurate (omega-1)-hydroxylating P450s, P450 2C2 and P450 2E1.

P450 2C2 as well as P450 2E1 [Fukuda, T. et al. (1993) J. Biochem. 113, 7-12] catalyzed the hydroxylation of medium chain fatty acids, although the regioselectivity of substrates of the former contrasted with that of the latter. Whereas P450 2E1 hydroxylated C9-C18 fatty acids at the omega-1 position and to a much lesser extent at the omega and omega-2 positions, P450 2C2 hydroxylated C9-C13 fatty acids at different positions dependent on the chain length of fatty acids. Among the fatty acids used as the substrate, undecanoate was hydroxylated at the omega-1 position almost exclusively by P450 2C2. The proportion of omega-hydroxylated products produced by P450 2C2 was markedly increased with decreasing chain length of fatty acids, while the hydroxylation positions were enlarged to the omega-3 position with tridecanoate. When the conserved Thr at the putative distal helix was replaced with Ser, the substrate regioselectivity of the two P450s was affected in different manners. The mutation of P450 2C2 did not change the hydroxylation positions of C9-C12 fatty acids, but caused a significant decrease in the proportion of the omega-1 hydroxy analog in the total products. In sharp contrast to P450 2C2, the mutated P450 2E1 gave additional products to those with the wild-type P450, and the number of different products increased with increasing chain length of the fatty acids. Thus, the products of palmitate hydroxylation were identified as omega-1, omega-2, omega-3, omega-4, omega-5, omega-6, and omega-7 monohydroxy isomers using gas chromatography-electron impact mass spectrometry.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

A major glucocorticoid-inducible P450 in rat liver is not P450 3A1.

A new P450 3A cDNA (RL33) has been cloned from a liver cDNA library of untreated male rat. RL33 is 2032 nucleotides in length and has an open reading frame of 502 amino acid residues. The nucleotide sequence of its 5'-noncoding region is completely identical with that of a genomic clone of P450 3A1 isolated by Burger et al. [Proc. Natl. Acad. Sci. USA 89, 2145-2149 (1992)]. Compared with rat P450 3A1, P450 RL33 showed 98 and 97% identities in the nucleotide and deduced amino acid sequences, respectively, with the deletion of 2 amino acids and substitution of 12 amino acids. These residues were localized around amino acids 107-230. Recently Kirita and Matsubara have isolated the same P450 3A cDNA (cDEX) from dexamethasone (DEX)-treated rat liver [Arch. Biochem. Biophys. 307, 253-258 (1993)]. Northern blot analysis using an oligonucleotide probe specific for P450 RL33/cDEX revealed that P450 RL33/cDEX mRNA was induced strongly by pregnenolone 16 alpha-carbonitrile and DEX and weakly by phenobarbital (PB) and triacetyloleandomycin. We constructed a P450 3A cDNA library by the reverse transcriptase-polymerase chain reaction using common primers to P450 RL33/cDEX, 3A1, and 3A2, and subcloned the cDNAs into pUC119. The expression level of P450 RL33/cDEX mRNA was investigated by identifying each clone with the above oligonucleotide probe. P450 RL33/cDEX mRNA represented over 70% of the total P450 3A mRNA from untreated, PB-, and DEX-treated rat liver. These results indicated that the major DEX-inducible form of P450 3A is P450 RL33/cDEX and not P450 3A1.

Amino Acid Sequence↗

PubMed1994

[Monocular indirect argon laser photocoagulation for advanced retinopathy of prematurity].

A retrospective study of monocular indirect argon laser retinal photocoagulation for retinopathy of prematurity (ROP) was performed on 53 eyes of 36 premature infants, admitted to the neonatal intensive care unit (NICU) of Juntendo hospital from Jan. 1988 to Dec. 1990. The argon laser beam was delivered from an argon laser source located in the outpatient clinic to the NICU through a 50-meter fiber-optic cable. Thirty-eight eyes of 27 infants showing stage 3 middle substage of ROP retained a mild grade of cicatrical ROP. Fifteen eyes of 8 infants showed "Plus disease". Five eyes of these retained a severe grade of cicatrical ROP. The success rate of ROP treatment by laser photocoagulation was more satisfactory than in xenon are photocoagulation with cryotherapy. This method has slight technical difficulties, but the infants could be treated in a supine position in the incubators. Thus, monocular indirect argon laser retinal photocoagulation is a useful method in the treatment of ROP.

Combined Modality Therapy↗

PubMed1993

A novel P450 expressed at the high level in rat brain.

Only P450 2D mRNA could be detected in Northern blot analysis of rat brain poly(A)+ RNA using probes from eight different P450s involved in drug metabolism. Four cerebral P450 cDNAs were isolated from a rat brain cDNA library using rat P450 2D2 cDNA as a probe, three of which were identified to rat P450 2D4. The expression of 2D4 mRNA was investigated by the reverse transcriptase-polymerase chain reaction and southern blot analysis using an oligonucleotide probe specific for P450 2D4. P450 2D4 mRNA was expressed at the high level in brain. Furthermore, it was detected in all other tissues examined, although to a lesser extent except in the liver and small intestine. However, total mRNAs of other P450 2D members (2D1, 2D2, 2D3, and 2D5) were mainly expressed in liver. The total level of expression of these mRNAs varied markedly among tissues. These results suggest that P450 2D4 may have a specific physiological function in the brain.

Animals↗

PubMed1993

Transgenic Drosophila carrying mammalian cytochrome P-4501A1: an application to toxicology testing.

Transgenic Drosophila which carry a canine cytochrome P-450 were established and evaluated for its value on toxicology testing. Dah1, a cDNA clone for the canine hepatic P-4501A1, was ligated between the promoter of Drosophila heat-shock protein gene and the terminator of actin 5C gene, and then microinjected into Drosophila embryos with a transposon P element. The injected DNA was stably integrated into chromosomal DNA in germ line cells. After heat-shock treatments, transgenic larvae produced mRNA and a detectable amount of protein that cross-reacted with antibodies against rat P-4501A1. The ability of transgenic flies to activate procarcinogens was monitored in the DNA repair test with the endpoint being preadult mortality of repair-defective mei-9a mei-41D5/Y males. Heat-shock treatments of larvae showed that the repair-defective males carrying the P-4501A1 transgene were killed by lower concentrations of 7,12-dimethylbenz[a]anthracene than their non-transgenic or non heat-shocked counterparts. Coadministration of alpha-naphthoflavone, one of the inhibitors of P-4501A subfamily, cancelled the enhanced mortality of transgenic males, supporting that 7,12-dimethylbenz[a]anthracene was metabolized to its genotoxic form by the expressed P-4501A1 enzyme. This study indicates a potential utility of transgenic Drosophila for screening mammalian promutagens and procarcinogens.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1993

Replacement of Thr-303 of P450 2E1 with serine modifies the regioselectivity of its fatty acid hydroxylase activity.

Threonine-303 of rabbit P450 2E1, which is putatively located at the distal heme surface, was replaced by serine and valine via site-directed mutagenesis. In the oxidized state, the Ser-mutated P450 exhibited a low- and high-spin mixed-type (low > high) absorption spectrum, whereas the Val-mutated P450, like the wild-type P450, exhibited a nearly high-spin type spectrum. The reduced CO complexes of the Ser- and Val-mutated P450s, as well as that of the wild-type P450, showed a Soret absorption maximum at 452 nm. Both mutated P450s were active in the hydroxylation of C10 to C18 fatty acids at somewhat lower rates than the wild-type P450. The Val-mutated P450 gave the same two products (the major one is probably the omega-1 hydroxy analog) as the wild-type P450, while additional products were formed on incubation with C11 to C17 fatty acids as substrates of the Ser-mutated P450; a total of four products was detected for each of the C12 to C15 fatty acids, and three for each of the C11, C16, and C17 homologues. The metabolites of laurate were determined by GC-MS analysis to be the omega-1, omega-2, omega-3, and omega-4 hydroxy counterparts. The Ser-mutated P450 hydroxylated drug substrates at almost the same rates as the wild-type P450, while the mutation to valine significantly lowered the drug hydroxylase activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Purification and characterization of a form of P450 from horse liver microsomes.

A form of P450 [termed P450(h-1)] was purified from the liver microsomes of a male horse to electrophoretic homogeneity. The specific content of the final P450(h-1) preparation was 14.8 nmol/mg of protein and the recovery was 0.38% of the microsomal P450. The apparent molecular weight of P450(h-1) was 52,000 Da. The absorption spectra of P450(h-1) indicated that P450(h-1) was a low- and high-spin mixed type P450 in the oxidized form. The reconstituted system containing P450(h-1) could catalyze benzphetamine N-demethylation, 7-ethoxycoumarin O-deethylation, and testosterone 16 alpha-hydroxylation. In the horse hepatic microsomes, aniline p-hydroxylation and testosterone 6 beta-hydroxylation, in addition to the above reactions, were detected. The N-terminal amino acid sequence of P450(h-1) was highly homologous to that of rat P450 2C11. Western blot analysis using anti-P450(h-1) antibody revealed that this antibody most strongly recognized P450 2C13 among ten rat P450s belonging to eight different subfamilies involved in hepatic drug metabolism. This anti-P450(h-1) antibody inhibited the testosterone 16 alpha-hydroxylase activity in horse liver microsomes. These results suggest that P450(h-1) belongs to the P450 2C subfamily and contributes to the testosterone 16 alpha-hydroxylation in horse liver microsomes.

Amino Acid Sequence↗

PubMed1993

[Relationship between lymphocyte subsets of the peripheral blood and noise induced hearing loss].

Biochemical examination and two-color flow cytometric analysis of lymphocyte subsets of the peripheral blood were carried out in 107 healthy males working in high noise environments. The level of hearing disorder was compared with these results. By audiometry at six frequency levels, 51 of the 107 healthy males showed hearing loss. Their mean value of hearing ability was 30 dB and/or above. Among the peripheral lymphocyte subsets, helper T cells of CD4+CD45R- were significantly increased and the CD4/CD8 ratio tended to be elevated. CD20 that indicate B cells were reduced. These results suggested a relationship between susceptibility to acoustic trauma and cell-mediated immunity.

Adult↗

PubMed1992

Molecular cloning of monkey liver cytochrome P-450 cDNAs: similarity of the primary sequences to human cytochromes P-450.

Three cDNAs coding for monkey cytochrome P-450 (P450) 2C, 2E and 3A (MKmp13, MKj1 and MKnf2, respectively) were isolated from a lambda gt11 cDNA library of a liver from a 3-methylcholanthrene (3MC)-treated crab-eating monkey, using cDNA fragments for human P450 2C, 2E and 3A as respective probes. MKmp13 and MKnf2 were 1901 and 2032 bp long, containing entire coding regions for polypeptides of 490 and 503 residues, respectively. The deduced N-terminal amino acid sequences of MKmp13 and MKnf2 were identical with those of P450-MK1 and P450-MK2, which had been purified from liver microsomes of untreated and polychlorinated biphenyl (PCB)-treated crab-eating monkeys, respectively. MKj1 was 1508 bp long, encoding a polypeptide of 449 residues, which is presumed to lack N-terminal 45 residues as compared with the sequence for human P450 2E1. Northern blot analysis indicated that monkey P450 2C, 2E and 3A mRNAs were expressed constitutively in monkey livers. P450 2E and 3A mRNAs were induced by both 3MC and PCB, while P450 2C mRNA was induced only by PCB. The deduced amino acid sequences of four monkey cytochrome P-450 cDNAs, including P450 1A1 (MKah1) which we isolated previously, were more than 92% identical with those of corresponding human cytochrome P-450 cDNAs.

Amino Acid Sequence↗

PubMed1992

Molecular cloning of monkey P450 1A1 cDNA and expression in yeast.

Monkey P450 1A1 cDNA (MKah1) was isolated from the lambda gt11 cDNA library of a liver from a 3-methylcholanthrene (3MC)-treated crab-eating monkey using a dog P450 1A1 cDNA fragment as a probe. MKah1 was 2453 bp long and contained an entire coding region for a polypeptide of 512 residues. The nucleotide and deduced amino acid sequences of MKah1 displayed 95% and 94% identity with those of the human P450 1A1 gene, respectively. Even in the 3' noncoding region, MKah1 showed 94% homology with human P450 1A1, whereas it showed less than 69% homology with other mammalian P450 1A1. Monkey P450 1A1 mRNA was not detectable in untreated livers, but was induced by polychlorinated biphenyl and 3MC. The expression plasmid (designated as pMKC-1) was constructed by introduction of the coding region of MKah1 into a yeast expression vector (pAM82) containing the promoter of acid phosphatase (APase). Northern blot analysis revealed that monkey P450 1A1 mRNA was expressed in yeast under the control of the APase promoter. Microsomes from yeast transformed by pMKC-1 catalyzed 7-ethoxycoumarin O-deethylation, benzo(a)pyrene hydroxylation and the mutagenic activation of 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ), 3-amino-1-methyl-5H-pyrido(4,3-b)-indole acetate (Trp-P-2) and 2-amino-6-methyldipyrido(1,2-a:3',2'-d)imidazole acetate (Glu-P-1).

Amino Acid Sequence↗